Testosterone, the main androgen present in bloodstream, acts directly on many target tissues, as such or as a reduced metabolite, i.e. dihydrotestosterone. The conversion into dihydrotestosterone is mediated by the enzyme 5-.alpha.-reductase, which is present in some target tissues. Dihydrotestosterone has a higher affinity to the androgen receptors than testosterone itself, moreover the hormone-receptor complex is more stable (Kaufman M., Pinsky L. J. Steroid Biochem. 1983, 18, 121-5; Wilbert D. M., Griffin J. E., Wilson J. D. J. Clin. Endocrinol. Metab. 1983, 56, 113-20). The inhibitors of the enzyme 5-.alpha.-reductase strongly bind to the enzyme, thus interfering in the transformation process of testosterone into dihydrotestosterone.
Up to now, a number of examples of inhibitors of the enzyme 5-.alpha.-reductase are known in literature; some having a steroidal structure (Rasmusson, G., H.; Reynolds, G. F.; Steimberg, N. G.; Walton, E.; Patel G. F.; Liang T.; Cacsieri M. A.; Cheung A. H.; Broocks J. R.; Berman C. Azasteroids: Structure-Activity Relationship for Inhibition of 5-.alpha.-Reductase and of Androgen Receptor Binding, J. Med. Chem. 1986, 29, 2298-2315. Holt D. A.; Levy M. A.; Oh H. J.; Erb J. M.; Heaslip J. I.; Brandt M.; Lan-Hargest H. Y.; Metcalf B. W. Inhibition of Steroid 5-.alpha.-Reductase by Unsaturated 3-Carboxysteroids, J. Med. Chem. 1990, 33, 943-950) other being nonsteroidal (EP 0 291 245 A2).
The pathologies connected with hyperandrogenicity conditions, in which these molecules might be used (benign prostatic hyperplasia, acne vulgaris, seborrhea, baldness, female hirsutism) are widespread. Though the therapy with this kind of medicaments proved to be effective, also as far as the life-quality offered to those suffering from said conditions is concerned, nevertheless it is not free from side-effects, therefore the development of novel, more potent inhibitors, which are more selective and better tolerated, is required (Charles D. J. et al. Nonsteroidal Inhibitors of Human Type 1 Steroid 5-.alpha.-Reductase, J. Med. Chem. 1993, 36, 421-423).
A 4-azasteroid conjugated at the 17.beta.-position with a .gamma.-amino acid (.gamma.-aminobutyric acid) is known from EP 0 271 220. In the above cited Patent, a procedure for the preparation of a certain number of compounds oxidized at the carbamoyl branching at the 17-position is claimed.